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문창기,박상준,조민구,김영중,김소연,김윤권,정준오,안석진,김은실,서승오,김지훈,최원제,이윤영,박형기,최규영,김현근 대한감염학회 2006 감염과 화학요법 Vol.38 No.6
Background: The purpose of this study was to document the incidence and clinical characteristics of patients with tuberculosis (TB) in combat and auxiliary police, living in a group, in Korea where the incidence rate of active TB in a general population is higher than in Western countries. Materials and Methods:We retrospectively reviewed the medical records of all tuberculosis patients diagnosed at National Police Hospital from January 2002 through December 2004. Results:In 2002-2004, a total of 156 cases of tuberculosis were identified with the mean (Standard deviation) age of 20.6 (±1.0) years. Of these, 134 (85.9%) patients were registered as new cases, 11 (7.1%) as relapse, 2 (1.3%) as failure, 5 (3.1%) as treatment-after-default cases whereas 4 (2.6 %) patients were not included in any categories. Average annual new TB rate and smear-positive TB rate were 86.5/10^(5) and 17.4/10^(5) person-years, respectively. In 12 of 31 smear-positive cases, time from onset of symptoms to diagnosis was more than 30 days. Two multidrug-resistance TB cases were identified and two suspected outbreak episodes of TB had occurred during 3 years. Conclusion:There was no statistically significant difference in the incidence rate of new cases of TB between the general population aged 20 to 29 years and combat and auxiliary police in Korea. 배경 : 국내 결핵의 발생은 감소 추세에 있으나 여전히 후진국형 발생양상을 보이고 있다. 특히 집단생활을 하는 젊은이들에서 발생하는 결핵의 유행이 간헐적으로 알려지고 있어 우려를 낳고 있다. 이에 저자들은 최근 전경대원의 결핵 발병 양상에 대해 알아보고자 본 연구를 시행하였다. 재료 및 방법 : 2002년 1월부터 2004년 12월까지 3년간 경찰병원에서 결핵 진료를 받은 전경대원의 의무기록을 후향적으로 분석하여 연도별 결핵 신환발생률, 도말양성결핵 신환율, 진단 지연, 집단발병, 다제내성결핵을 조사하였다. 결과 : 연도별 결핵 신환자 수(10만명당 발생추정치)는 2002년 50명(83.6명), 2003년 42명(83.7명), 2004년 42명(93.5명)이었고 도말양성 폐결핵 신환자 수는 2002년 10명(16.7명), 2003년 11명(21.9명), 2004년 6명(13.4명)이었다. 3년간 도말양성 폐결핵 환자는 31명이 있었고 그 중 12명은 호흡기 증상 발생 30일이 지나서 진단을 받았다. 다제내성 결핵은 2명이 있었으며 결핵의 집단발병이 의심되는 사례는 2차례 있었다. 결론 : 전경대원과 20-29세 연령군 일반인의 결핵 신환발생률, 도말양성 폐결핵 발생률의 통계적으로 유의한 차이는 없었다.
Yoon, Young-Sil,Yoon, Dong-Sun,Lim, In Kyoung,Yoon, Soo-Han,Chung, Hae-Young,Rojo, Manuel,Malka, Florence,Jou, Mei-Jie,Martinou, Jean-Claude,Yoon, Gyesoon Liss 2006 Journal of Cellular Physiology Vol.209 No.2
<P>Enlarged or giant mitochondria have often been documented in aged tissues although their role and underlying mechanism remain unclear. We report here how highly elongated giant mitochondria are formed in and related to the senescent arrest. The mitochondrial morphology was progressively changed to a highly elongated form during deferoxamine (DFO)-induced senescent arrest of Chang cells, accompanied by increase of intracellular ROS level and decrease of mtDNA content. Interestingly, under exposure to subcytotoxic doses of H<SUB>2</SUB>O<SUB>2</SUB> (200 µM), about 65% of Chang cells harbored elongated mitochondria with senescent phenotypes whereas ethidium bromide (EtBr) (50 ng/ml) only reformed the cristae structure. Elongated giant mitochondria were also observed in TGF β1- or H<SUB>2</SUB>O<SUB>2</SUB>-induced senescent Mv1Lu cells and in old human diploid fibroblasts (HDFs). In all senescent progresses employed in this study Fis1 protein, a mitochondrial fission modulator, was commonly downexpressed. Overexpression of YFP-Fis1 reversed both mitochondrial elongation and appearance of senescent phenotypes induced by DFO, implying its critical involvement in the arrest. Finally, we found that direct induction of mitochondrial elongation by blocking mitochondrial fission process with Fis1-ΔTM or Drp1-K38A was sufficient to develop senescent phenotypes with increased ROS production. These data suggest that mitochondrial elongation may play an important role as a mediator in stress-induced premature senescence. J. Cell. Physiol. 209: 468–480, 2006. © 2006 Wiley-Liss, Inc.</P>
Yoon, Seokho,An, Young-Sil,Lee, Su Jin,So, Eu Young,Kim, Jang-Hee,Chung, Yoon-Sok,Yoon, Joon-Kee Wolters Kluwer Health 2015 Medicine Vol.94 No.48
<P><B>Abstract</B></P><P><I>BRAFV</I>600E mutation and F-18 fluorodeoxyglucose (FDG) uptake are potential prognostic factors of papillary thyroid cancer (PTC). This study was performed to investigate the relationship between the <I>BRAFV</I>600E mutation and F-18 FDG uptake in PTC.</P><P>We retrospectively included 169 PTC patients who underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) before thyroidectomy from May 2009 to August 2012. Subjects were classified into overt PTC (>1 cm, n = 76) and papillary thyroid microcarcinoma (PTMC, n = 93) groups. Univariate and multivariate analyses were performed to assess the relationship between maximum standardized uptake value (SUV<SUB>max</SUB>) of the primary tumors and clinicopathologic variables.</P><P>The <I>BRAFV</I>600E mutation was detected in 82.2% (139/169). In all subjects, the <I>BRAFV</I>600E mutation and tumor size were independently related to SUV<SUB>max</SUB> by multivariate analysis (<I>P</I> = 0.048 and <I>P</I> < 0.001, respectively). SUV<SUB>max</SUB> was significantly higher in tumors with the <I>BRAFV</I>600E mutation than in those with wild-type <I>BRAF</I> (9.4 ± 10.9 vs 5.0 ± 4.1, <I>P</I> < 0.001). Similarly, in overt PTC group, the <I>BRAFV</I>600E mutation and tumor size were independently correlated with SUV<SUB>max</SUB> (<I>P</I> = 0.032 and <I>P</I> = 0.001, respectively). By contrast, in PTMC group, only tumor size was significantly associated with SUV<SUB>max</SUB> (<I>P</I> = 0.010).</P><P>The presence of the <I>BRAFV</I>600E mutation is independently associated with high F-18 FDG uptake on preoperative PET/CT in patients with overt PTC, but this relationship was not evident in PTMC. This study provides a better understanding of the relationship between F-18 FDG uptake and <I>BRAFV</I>600E mutation in patients with PTC.</P>
Young Sil Lee,Kwan Han Yoon 한국탄소학회 2015 Carbon Letters Vol.16 No.2
Multi-walled carbon nanotube (MWCNT)/polycarbonate (PC) nanocomposite was prepared by direct melt mixing to investigate the effect of the shear rate on the surface resistivity of the nanocomposites. In this study, an experiment was carried out to observe the shear induced orientation of the MWCNT in the polymer matrix using a very simple melt flow indexer with various loads. The compression-molded, should be eliminated. MWCNT/PC nanocomposite sample exhibited lower percolation thresholds (at 0.8 vol%) and higher electrical conductivity values than those of samples extruded by capillary and injection molding. Shear induced orientation of MWCNT was observed via scanning electron microscopy, in the direction of flow in a PC matrix during the extrusion process. The surface resistivity rose with increasing shear rate, because of the breakdown of the network junctions between MWCNTs. For real applications such as injection molding and the extrusion process, the amount of the MWCNT in the composite should be carefully selected to adjust the electrical conductivity.
cAMP-inducible coactivator CRTC3 attenuates brown adipose tissue thermogenesis
Yoon, Young-Sil,Tsai, Wen-Wei,Van de Velde, Sam,Chen, Zhijiang,Lee, Kuo-Fen,Morgan, Donald A.,Rahmouni, Kamal,Matsumura, Shigenobu,Wiater, Ezra,Song, Youngsup,Montminy, Marc National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.23
<P>In response to cold exposure, placental mammals maintain body temperature by increasing sympathetic nerve activity in brown adipose tissue (BAT). Triggering of beta-adrenergic receptors on brown adipocytes stimulates thermogenesis via induction of the cAMP/PKA pathway. Although cAMP response element-binding protein (CREB) and its coactivators-the cAMP-regulated transcriptional coactivators (CRTCs)-mediate transcriptional effects of cAMP in most tissues, other transcription factors such as ATF2 appear critical for induction of thermogenic genes by cAMP in BAT. Brown adipocytes arise from Myf5-positive mesenchymal cells under the control of PRDM16, a coactivator that concurrently represses differentiation along the skeletal muscle lineage. Here, we show that the CREB coactivator CRTC3 is part of an inhibitory feedback pathway that antagonizes PRDM16-dependent differentiation. Mice with a knockout of CRTC3 in BAT (BKO) have increased cold tolerance and reduced adiposity, whereas mice overexpressing constitutively active CRTC3 in adipose tissue are more cold sensitive and have greater fat mass. CRTC3 reduced sympathetic nerve activity in BAT by up-regulating the expression of miR-206, a microRNA that promotes differentiation along the myogenic lineage and that we show here decreases the expression of VEGFA and neurotrophins critical for BAT innervation and vascularization. Sympathetic nerve activity to BAT was enhanced in BKO mice, leading to increases in catecholamine signaling that stimulated energy expenditure. As reexpression of miR-206 in BAT from BKO mice reversed the salutary effects of CRTC3 depletion on cold tolerance, our studies suggest that small-molecule inhibitors against this coactivator may provide therapeutic benefit to overweight individuals.</P>
Young-sil Yoon,Choul-gyun Lee 한국생물공학회 2009 Biotechnology and Bioprocess Engineering Vol.14 No.4
The antifungal compound AK-3 is purified and characterized from intracellular metabolites of the unicellular cyanobacteria, Synechocystis sp. PCC 6803. AK-3 clearly had antifungal effects upon growth of the fungi Aspergillus spp. From 2 g of dry cell powder, 4.8 mg of AK-3 was obtained with a yield of 0.24%. Its structure was elucidated by NMR, UV spectra, amino acid analysis by chemical degradation, and MS measurements, including MALDI-TOF and MS-MS techniques. AK-3 contains a high level of antifungal activity compared to itraconazole and is seemingly a new compound based on its amino acid composition. Extraction was performed with an acetic acid/water mixture (pH 3.0) while detection at UV 214 nm found AK-3 did not react with ninhydrin. These results suggest that this compound is a cyclic peptide with high hydrophilicity and a phenolic ring.
N-Methyl Amine-substituted Fluoxetine Derivatives: New Dopamine Transporter Inhibitors
Young Sil Yoon,Taesup Cho,Sung-Hwa Yoon,Churl Ki Min,Changho Lee 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.12
Transport of dopamine (DA) by the dopamine transporter from the synaptic cleft into the presynaptic terminals plays a key role in terminating dopaminergic neurotransmission. The binding of psychostimulants to their recognition sites on the DA transporter leads to an inhibition of DA transport and a subsequent rising of the dopamine contents in the synaptic cleft is ascribed to a mode of psychostimulation. Discovery of dopamine transporter inhibitors would be useful with regard to substituting for cocaine and minimizing its abuse. Recently, a number of fluoxetine analogues were synthesized, especially focusing on the substitution of N-methyl amine group through modifying the structure of the fluoxetine, N-methyl-3-[p-trifluoromethylphenoxy]-3-phenylpropylamine, widely used as an antidepressant. Among them, the pharmacological properties of FD-2, (R)-N-ethanol-3-(4-trifluorophenoxy)-3-phenyl propaneamine and FD-4, N-(R)-3-trifluorophenoxy-3-phenylpropane-imidazole with a higher affinity for the DA transporter were characterized in terms of dopamine transporter inhibition expecting for useful cocaine substitutes. Effects of the compounds on [H3]dopamine uptake, [I125]RTI-55 binding, and DA transporter-associated currents were examined with the ligand binding assays and voltage clamping technique in human embryonic kidney (HEK)-293 cells where the recombinant human DA transporter (hDAT) was stably expressed. Our results showed that (i) fluoxetine was potent in inhibiting both the uptake of [H3]DA (IC50 = 0.21 ± 0.032 mM, n = 3) and the [I125]RTI-55 binding (IC50 = 0.23 ± 0.012 mM, n = 10); (ii) N-methyl amine substituted fluoxetine analogues, FD-2 and FD-4 were equally or more potent than fluoxetine itself in terms of inhibition of [H3]DA uptake (IC50 FD-2: 0.077 ± 0.0032 mM (n = 3); FD-4: 0.26 ± 0.13 mM (n = 3), inhibition of [I125]RTI-55 binding, and reduction in DA transporter-associated currents, suggesting that these analogues could be a new class of dopamine transporter inhibitors.
Salt-inducible kinase regulates hepatic lipogenesis by controlling SREBP-1c phosphorylation.
Yoon, Young-Sil,Seo, Woo-Young,Lee, Min-Woo,Kim, Seong-Tae,Koo, Seung-Hoi American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.16
<P>Liver plays a major role in regulating energy homeostasis in mammals. During feeding conditions, excessive glucose is converted into a preferred storage form of energy sources as triacylglycerol in liver via a collective metabolic pathway termed lipogenesis. Sterol regulatory element-binding protein 1c is a master regulator for this process by activating number of enzyme genes, such as Fasn or Acaca, that are involved in this pathway at the transcriptional level. Here we show that the salt-inducible kinase (SIK) family of proteins regulates the hepatic lipogenesis by modulating SREBP-1c activity. Overexpression of SIK1 inhibits hepatic expression of lipogenic genes, such as Fasn, whereas knockdown of SIK1 in liver greatly enhances their expression. Regulation of the Fasn gene by SIK kinases is mediated at the level of transcription via phosphorylation and inactivation of nuclear SREBP-1c. Among candidate sites for SIK-dependent regulation of SREBP-1c, the serine 329 residue is shown to be a critical regulatory site for SIK-mediated repression of SREBP-1c activity by in vitro kinase assay and reverse transcription-PCR analysis in primary hepatocytes. Finally, reduced hepatic triacylglycerol levels and lipogenic gene expression by adenoviral SIK1 transgenic expression are restored to normal levels by co-infection of mutant SREBP-1c, suggesting that SIK-dependent regulation of hepatic lipogenesis is indeed mediated through the phosphorylation of SREBP-1c in vivo. The process for the development of nonalcoholic fatty liver involves de novo lipogenesis via the activation of SREBP-1c. Modulation of SREBP-1c activity by SIK proteins would provide an attractive means for the regulation of such diseases.</P>